The Disease, Porphyromonas gingivalis, and Disease Process
The tissue affected by periodontitis may include the gingival tissue (gums); periodontal membrane (connective tissue embedded in the cementum and alveolar bone); cementum (mineralized connective tissue covering the roots of the teeth); and the alveolar bone (bone socket). Depending on the progression of the disease, there may occur a destruction of periodontal membranes, alveolar bone loss, and apical migration of the connective tissue attachment. Advanced periodontal disease may result in the formation of periodontal pockets harboring bacterial plaque, and progressive loosening and eventual loss of teeth.
Porphyromonas gingivalis is a black-pigmented anaerobe that is considered to be a major pathogenic species of Gram-negative subgingival flora. P. gingivalis is associated with several periodontal diseases including adult periodontitis, generalized juvenile periodontitis, periodontal abscesses, and refractory periodontitis. The association between P. gingivalis and periodontal disease suggests that components of P. gingivalis may be useful in strategies to reduce the incidence, and to prevent the development of periodontal disease caused by this pathogen. Initiation of the disease process and subsequent progression is thought to be dependent on the interaction between host factors and bacterial virulence factors which includes the processes of access to host tissue, adherence and colonization, and mediation of tissue destruction.
In developing compositions which could be used for prophylactic treatment of periodontitis, it would be desirable for the compositions to interfere with the initial stages of the disease process, such as adherence to host mucosal surfaces. P. gingivalis adheres to a variety of surfaces including epithelial cell surface receptors, salivary components, and other attached bacteria. Components of P. gingivalis thought to be involved in adhesion include fimbriae, vesicles, and hemagglutinins. Fimbrial protein of P. gingivalis has been purified which facilitates the study of the role of fimbriae in adhesion (Sojar et al., 1991, Biochem. Biophys. Res. Commun. 175:713-719, hereby incorporated by reference). A 43 kilodalton (kDa) protein has been purified from P. gingivalis and has been shown to be a major fimbrillin monomer subunit of fimbriae. Studies using different strains of P. gingivalis, obtained from a wide geographic distribution, showed immunological cross-reactivity as well as strain-specific antigens (Lee et al., 1991, Infect. Immun. 59:383-389). Although these studies suggest that there is some antigenic conservation among strains of fimbriated P. gingivalis, it was not known whether the conserved antigens are important in a host immune response protective against the bacteria, and/or constitute domains which function in adherence by the bacteria.